We have developed an immunotoxin SS1P that targets ovarian cancers, mesotheliomas and pancreatic cancers that is currently in clinical trials. We are carrying out laboratory experiments to produce improved forms of SS1P that are less immunogenic so that several treatment cycles can be given. We have also investigated how to improve the activity of SS1P against solid tumors and found that if chemotherapy is give before SS1P there is profound synergy. We are investigating the mechanism of this synergy. We have studied mesothelin expression in lung cancer and demonstrated lung cancer cells are good targets for SS1P therapy. We have produced less immunogenic immunotoxins by mutating amino acids on the surface of PE38 to alenine or glycine. We are determining the pathway that toxins use to induce apoptosis.